Handheld pipettes, which are used for precision fluid volume measurement and delivery, are some of the most common and widely-used laboratory tools available to scientists today. Nearly all low-volume fluid handling of biological and chemical liquid samples rely on their ease of use, precision and repeatability to ensure proper, consistent experimental processing. Commercial pipettes are available in a wide variety of fixed and adjustable volumes. When used in large-scale, high-throughput testing, commercially available pipettes are often multiple-channel, allowing for precise fluid metering of up to 12 different samples, simultaneously, with the single push of a button. Typical pipette instruments rely on positive displacement systems (e.g. either a manually operated plunger system, or an electronic pump) to generate the pressure required to urge a specified fluid volume into, or out of, a disposable pipette tip. Once the sample is ejected, the pipette tip is discarded. State-of-the-art pipette instruments are capable of accurately metering fluid volumes of less than 1 mL, and employ servo pumps for volume control and fluid metering. Digital displays with integrated electronic controls improve the pipette instrument's ease of use for the operator.
In the laboratory, pipettes are found in wet bench environments and are used in countless fluid-metering applications ranging from fluid mixing to sample isolation and preparation. In experimental cell biology, pipettes are routinely used to isolate small volume suspensions of cells in culture. In one of the most common procedures, manually counting (under microscope observation) a small portion of the cells in a precisely metered volume allows a user to make population and cell viability estimates for the entire volume of cells in culture. Unfortunately, counting cells under a microscope using this approach is very time and resource intensive, and count accuracy depends wholly on the number of cells a user is willing to actually count in the given volume.
Pioneering work in particle detection by measuring impedance deviation caused by particles flowing through a small aperture between two containers of electrically conductive fluids is disclosed in U.S. Pat. No. 2,656,508 to W. H, Coulter. The inventor's name is now associated with the principle of particles causing a change in electric impedance as they occlude a portion of the aperture. Since publication of his patent, considerable effort has been devoted to developing and refining sensing devices operating under the Coulter principle. Relevant US patents include U.S. Pat. No. 5,376,878 to Fisher, U.S. Pat. No. 6,703,819 to Gascoyne et al., U.S. Pat. No. 6,437,551 to Krulevitch et al., U.S. Pat. No. 6,426,615 to Mehta, U.S. Pat. No. 6,169,394 to Frazier et al., U.S. Pat. Nos. 6,454,945 and 6,488,896 to Weigl et al., U.S. Pat. No. 6,656,431 to Holl et al., and U.S. Pat. No. 6,794,877 to Blomberg et al. All of the above-referenced documents are hereby incorporated by reference, as though set forth herein in their entireties, for their disclosures of technology and various sensor arrangements.
It would be an improvement to provide a precision fluid interrogation device that is capable of metering very precise quantities of a fluid to form a sample, and electrically interrogating that sample to determine one or more characteristic, such as particle count per unit volume. It would be a further advance for the apparatus to be embodied as a low-cost, one-time-use, rugged, and disposable device.